Lecture notes
ANTI EMETIC DRUGS
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High yield notes of anti emetic drugs.
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D2 RECEPTOR ANTAGONISTS1. Substituted benzamides:
Metoclopramide.
Mechanism D2 receptor antagonist. Potent antiemetic and prokinetic drug. As antiemetic
blocks D2 receptors on CTZ. As prokinetic stimulates gut motor function.
Increase resting tone, contractility, LES tone, motility, promotes gastric
emptying.
Excreted in urine and breast milk.
Clinical Use Antiemetic, Diabetic and postoperative gastroparesis ( impaired gastric
emptying ), persistent GERD, Postpartum lactation stimulation ( increases
prolactin levels ). Symptomatic treatment of non-ulcer dyspepsia.
Adverse 1. Extrapyramidal symptoms: ↑ parkinsonian effects, tardive dyskinesia,
effects restlessness, drowsiness, fatigue, depression. ( Due to central dopamine
receptor blockade ).
2. Bowel upsets: Diarrhea.
Drug interaction with digoxin and diabetic agents. Contraindicated in
patients with small bowel obstruction, Parkinson disease (due to D2 -
receptor blockade), ↓ seizure threshold.
2. Butyrophenones Droperidol, Haloperidol, Domperidone.
A. Droperidol
Mechanism Central D2 receptor antagonist
Clinical Use It had been used most often for sedation in endoscopy and surgery, usually
in combination with opioids or benzodiazepines.
Adverse Extra pyramidal symptoms, postural hypotension, QT interval prolongation.
Effects
, B. Domperidone
Mechanism Doesn’t cross BBB, only acts on D2 receptors in CTZ where BBB is leaky.
Clinical Use Used in nausea and vomiting. No extra pyramidal symptoms. Used as
antiemetic, prokinetic agent and for postpartum lactation stimulation.
High-dose haloperidol was found to be nearly as effective as high-dose metoclopramide
in preventing cisplatin-induced emesis.
3. Phenothiazines
Prochlorperazine, Promethazine, Thiethylperazine.
Phenothiazines are antipsychotics with potent antiemetic property due to d2 antagonism
and antimuscarinic properties.
Sedative property due to antihistaminic effects.
Mainly used as antiemetic in severe nausea and vomiting.
Main adverse effects: Extra pyramidal symptoms, sedation, postural hypotension.
Prochlorperazine is effective against low or moderately emetogenic chemotherapeutic
agents ( for example, fluorouracil and doxorubicin ).
BENZODIAZEPINES
Diazepam, lorazepam, alprazolam
Antiemetic potency is low.
Effects may be due to their sedative, anxiolytic, and amnesic properties.
Benzodiazepines useful in treating anticipatory vomiting.
Anticipatory nausea and vomiting is caused by triggers, such as the sights, smells and
anxiety.
Concomitant use of alcohol should be avoided due to additive CNS depressant effects.
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